Inflammation-associated (postinflammatory) hyperpigmentation (IAH) is a common problem in dermatologic practice, but the pathophysiology is not well understood. Kit protein, the receptor for stem cell factor (SCF), is a receptor tyrosine kinase expressed by melanocytes. Kit activation stimulates melanin production by melanocytes, and we hypothesize that it is involved in the pathogenesis of IAH. Transgenic mice expressing epidermal SCF controlled by a human keratin 14 (HK14) promoter have intraepidermal melanocytes and melanin, unlike nontransgenic mice, and may spontaneously develop IAH in old age. Our specific aims are (1) to establish a murine model of IAH by using HK14- SCF transgenic mice and irritant and allergic contactants; (2) to examine the effects of therapies currently used for human IAH, such as tretinoin and hydroquinone, in this mode of IAH; and (3) to test our hypothesis that SCF contributes to IAH by blocking the development of IAH with tyrosine kinase inhibitors which specifically inhibit kit function. Data generated from these experiments will expand our understanding of the pathophysiology of IAH and lead to the development of novel therapeutic approaches.